Experiments will be designed, using techniqus of adoptive immunization, to characterize the defects in the hosts immune response that are associated with non-healing metastatic disease. This will involve the admixing of "immune" cells from donors exhibiting solid immunity, with various populations of lymphoid cells from animals with metastatic disease in which resistance has waned. Such mixtures will be infused into normal guinea pigs and the subsequent ability of these animals to remove a standard challenge with L. enriettii will be tested. Further experiments will be aimed at examining macrophage/parasite interaction, with particular emphasis being placed on determining the mechanism whereby parasites within macrophages are protected from the immune mechanisms of the host. This approach will include in vitro experiments in which the survival of L. enriettii will be assessed in an environment designed to allow the interaction of macrophages, lymphoid cells and/or serum factors. To allow objective evaluation of such experiments an assay method, involving the use of isotopically labelled parasites, will be used to measure the destruction of Leishmania. Considerable attention will be given to examining the local environment at metastatic foci of infection to try and determine why acquired resistance is not expressed at these sites.